Intensified Chemo-immuno-radiotherapy With Durvalumab for Stage III Non-Small Cell Lung Cancers

NCT ID: NCT04230408

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-05
• Study Completion Date: 2024-12-20

Brief Summary

This is a phase II study that will assess if Durvalumab (MEDI4736) used as induction chemo-immunotherapy followed by concurrent chemo-immuno-radiotherapy and consolidation immunotherapy may improve oncologic outcomes compared with standard of care chemoradiation followed by durvalumab (as in the PACIFIC trial) with a reasonable safety profile.

Detailed Description

Prospective, non-randomized, open label, single arm, multi-institutional, phase 2 study, including patients with stage III non-small cell lung cancer able to receive concurrent chemoradiation. Eligible patients will then receive treatment as follows:

Induction chemo-immunotherapy Two 21-day cycles of carboplatin, paclitaxel and durvalumab will be given BEFORE concurrent chemo-immuno-radiotherapy.

Thereafter, patients without progressive disease (or patients with disease progression that is still locally advanced and can be safely encompassed within tolerable radiation fields) will receive concurrent chemo-immuno-radiotherapy, as follows:

Concurrent chemo-immuno-radiotherapy Concurrent carboplatin, paclitaxel, and durvalumab with radiation therapy, initiated preferably 3-5 weeks after the last dose of induction chemo-immunotherapy.

Thereafter, patients without progressive disease will receive consolidation immunotherapy, as follows:

Consolidation immunotherapy Twelve 28-day cycles of durvalumab will be given, initiated preferably within one week following concurrent chemo-immuno-radiotherapy.

Conditions

Lung Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DURVALUMAB (MEDI4736) + carboplatin-paclitaxel

Induction chemo-immunotherapy phase:

Two cycles of Paclitaxel 200 mg/m2, Carboplatin AUC 6 and Durvalumab 1500 mg intravenously every 21 days.

Concurrent chemo-immuno-radiotherapy phase:

Radiation therapy concomitantly with: paclitaxel 50 mg/m2 intravenously every 7 days (+/- 3 days) until completion of radiation therapy, carboplatin AUC 2 intravenously every 7 days (+/- 3 days) until completion of radiation therapy and durvalumab 1500 mg intravenously every 21 days (+/- 6 days) for a maximum of 2 doses.

Concurrent chemo-immuno-radiotherapy:

Durvalumab 1500 mg intravenously every 28 days (+/- 7 days) for a maximum of 12 doses

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation

Interventions

Durvalumab

Intensified chemo-immuno-radiotherapy with durvalumab in combination with carboplatin, paclitaxel and radiation

Intervention Type: DRUG

Other Intervention Names

Carboplatin; Paclitaxel

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed non-small cell lung cancer.

2. Stage III according to the American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition.

3. No prior systemic therapy, radiation therapy, or surgery for the current cancer.

4. Age ≥ 18 years at time of study entry

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Body weight >30kg

7. Pre- or post-bronchodilator forced expiratory volume 1 ≥ 1.2 litres/second or ≥ 50% of predicted value

8. Adequate normal organ and marrow function

8. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

9. Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.

10. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 antibodies

11. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.

12. Prior radiation therapy to the region of the study cancer that would result in overlap of radiation therapy fields.

13. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of the investigational product.

14. Active or prior documented autoimmune or inflammatory disorders

15. Uncontrolled intercurrent illness

16. History of another primary malignancy

17. Known active infection including tuberculosis , hepatitis B, hepatitis C, or human immunodeficiency virus.

Exclusion Criteria

1. Patients whose radiation treatment is likely to encompass a volume of whole lung receiving ≥ 20 Gy in total of more than 35% of lung volume.

2. Patients whose radiation treatment is likely to deliver a cardiac dose V50 > 25%

3. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

4. Participation in another clinical study with an investigational product with anti-neoplastic activity during the last 3 weeks prior to treatment initiation

5. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

6. History of allogenic organ transplantation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Libbs Farmacêutica LTDA

INDUSTRY

Sponsor Role: collaborator

Latin American Cooperative Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Liga Norte Riograndense Contra o Câncer

Natal, Rio Grande do Norte, Brazil

CPO

Porto Alegre, Rio Grande do Sul, Brazil

COI Américas

Rio de Janeiro, , Brazil

Beneficiencia Portuguesa de São Paulo/Hospital São José

São Paulo, , Brazil

ICESP

São Paulo, , Brazil

Countries

Brazil

Other Identifiers

LACOG 2218

Identifier Type: -

Identifier Source: org_study_id